Cathepsin D degrader 1
Anti-hepatic fibrosis agent 3 is an orally active anti-hepatic fibrosis compound targeting Cathepsin D. Anti-hepatic fibrosis agent 3 shows an IC50 of 53.18 μM against COL1A1-promoter and a Kd of 8.86 μM for binding to Cathepsin D. Anti-hepatic fibrosis agent 3 directly binds to and promotes the degradation of Cathepsin D, with no significant effect on Cathepsin B or Cathepsin L. Anti-hepatic fibrosis agent 3 inhibits hepatic stellate cell activation and reduces extracellular matrix deposition and inflammatory cytokine expression. Anti-hepatic fibrosis agent 3 exhibits remarkable anti-fibrotic activity in rat BDL and mouse CDAHFD-induced hepatic fibrosis models. Anti-hepatic fibrosis agent 3 can be used for the study of hepatic fibrosis.
For research use only. We do not sell to patients.
- CAS No.: 3127060-85-6
- Formula: C22H28N2O3
- Molecular Weight:368.47
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Biological Activity
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Chemical Information
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Biological Activity
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Cathepsin D 8.86 μM (Kd) |
Anti-hepatic fibrosis agent 3 (compound 9a) potently inhibits COL1A1-promoter activity in LX-2 cells with an IC50 of 53.18 μM and a selectivity index of 3.60[1].
Anti-hepatic fibrosis agent 3 (20-80 μM; 24 h) inhibits fibrogenic marker proteins (COL1A1, fibronectin, α-SMA, p-Smad2) and suppresses fibrosis-related gene mRNA levels (COL1A1, fibronectin, TGFB1, MMP2, ACTA2, TIMP1) TGFβ1-induced LX-2 cells, and reduces fibrogenic protein expression in mouse hepatic stellate cells (mHSC) in a concentration-dependent manner[1].
Anti-hepatic fibrosis agent 3 (20-80 μM; 24 h) dose-dependently downregulates pro-Cathepsin D and Cathepsin D protein levels with no effect on Cathepsin B and Cathepsin L in LX-2 and mHSC cells, and decreases inflammatory protein expression (IL-1β, caspase-1) in Lipopolysaccharides (HY-D1056)-stimulated LX-2 and mHSC cells[1].
Anti-hepatic fibrosis agent 3 (80 μM; 6-48 h) accelerates the degradation of pro-Cathepsin D and Cathepsin D in Cycloheximide (HY-12320)-pretreated LX-2 cells<[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LX-2 cells
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Concentration:20 μM, 40 μM, 80 μM
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Incubation Time:24 h
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Result:Dose-dependently downregulates the mRNA levels of fibrosis-related genes (COL1A1, fibronectin, TGFB1, MMP2, ACTA2, TIMP1).
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Cell Line:Cycloheximide (CHX)-pretreated LX-2 cells
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Concentration:80 μM
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Incubation Time:6 h, 12 h, 24 h, 36 h, 48 h
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Result:Significantly accelerated the degradation of pro-Cathepsin D and Cathepsin D.
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Cell Line:LPS-stimulated LX-2 cells, LPS-stimulated mHSC
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Concentration:20 μM, 40 μM, 80 μM
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Incubation Time:24 h
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Result:Significantly decreased the protein levels of inflammatory factors IL-1β and caspase-1.
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Cell Line:LX-2 cells, mouse hepatic stellate cells (mHSC)
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Concentration:20 μM, 40 μM, 80 μM
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Incubation Time:24 h
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Result:Dose-dependently downregulated the protein levels of Cathepsin D, pro-Cathepsin D, COL1A1, fibronectin, α-SMA and p-Smad2, and showed no significant effect on Cathepsin B and Cathepsin L.
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Cell Line:TGFβ1-stimulated LX-2 cells
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Concentration:Anti-hepatic fibrosis agent 3 (20 μM, 40 μM, 80 μM), L-theanine (20 μM, 40 μM, 80 μM)
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Incubation Time:24 h
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Result:Dose-dependently downregulates fibrosis-related proteins (COL1A1, fibronectin, α-SMA, p-Smad2, MMP2, TGFβ1, CTGF, TIMP1); exhibits stronger inhibitory activity than L-theanine and most tested analogs.
Anti-hepatic fibrosis agent 3 (100-200 mg/kg; p.o.; daily; 4 weeks) dose-dependently ameliorates CDAHFD-induced metabolic hepatic fibrosis and inflammation in C57BL/6 mice, with significant improvements in serum liver injury markers, reductions in collagen deposition, fibrotic and inflammatory biomarker expression, and Cathepsin D levels at doses of 100 mg/kg and 200 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male, 180-200 g, BDL surgery-induced hepatic fibrosis)[1]
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Dosage:100 mg/kg; 200 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Significantly reduced serum levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and total bilirubin (TBIL) in a dose-dependent manner.
Improved liver elasticity and surface smoothness compared to BDL model group.
Reduced liver injury and collagen deposition in a dose-dependent manner via histological analysis; significantly reduced hepatic necrosis at 200 mg/kg dose.
Significantly reduced liver hydroxyproline content in 200 mg/kg dose group.
Downregulated protein levels of fibrotic biomarkers (Fibronectin, COL1A1, α-SMA, TGFβ1, CTGF, TIMP1) in liver tissue in a dose-dependent manner.
Downregulated mRNA levels of Col1a1 and Acta2 in 200 mg/kg dose group.
Reduced protein levels of pro-Cathepsin D and Cathepsin D in liver tissue in a dose-dependent manner.
Inhibited protein and mRNA expression of pro-inflammatory factors (IL-6, IL-1β) and reduced inflammation score in pathological sections in a dose-dependent manner.
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Animal Model:C57BL/6 (8-week-old, CDAHFD feeding-induced hepatic fibrosis)[1]
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Dosage:100 mg/kg; 200 mg/kg
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Administration:p.o.; daily; 4 weeks
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Result:Improved serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) in a dose-dependent manner, with greater efficacy than positive control OCA for ALT and ALP.
Partially restored hepatic luster and elasticity compared to CDAHFD model group.
Reduced hepatic ballooning degeneration and collagen deposition via histological analysis; reduced hepatic fibrosis scores in a dose-dependent manner via semiquantitative scoring.
Significantly reduced liver hydroxyproline content in both dose groups.
Downregulated protein levels of fibrotic biomarkers (COL1A1, Fibronectin, α-SMA) and mRNA levels of Col1a1, Mmp2, Timp1, and Acta2 in liver tissue.
Reduced protein levels of pro-Cathepsin D and Cathepsin D in liver tissue in a dose-dependent manner.
Inhibited protein and mRNA expression of pro-inflammatory factor (IL-6) in a dose-dependent manner.
Chemical Information
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CAS No. 3127060-85-6
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Molecular Weight 368.47
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Formula C22H28N2O3
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SMILES
O=C(OC)[C@H](CCC(NCC)=O)N(CC1=CC=CC=C1)CC2=CC=CC=C2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
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Data Sheet (280 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Cathepsin D degrader 1 Related Classifications
HY-181655 Related Classifications
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